胶质细胞瘤复发前后Cyclin D1和P16的表达

目的　探讨CyclinD1,P16在胶质瘤复发前后表达改变及其意义。方法　采用免疫组织化学LsABC法对 4 5例复发胶质瘤瘤组织、瘤旁脑组织和 10例正常脑组织CyclinD1,P16蛋白表达进行检测 ,统计分析CyclinD1,P16表达水平与胶质瘤分级、肿瘤复发的关系。结果　正常脑组织 ,瘤旁脑组织和胶质瘤组织CyclinD1表达依次升高 ,而P16的表达依次下降 ;肿瘤复发CyclinD1表达增强 ,P16的表达减弱。结论　CyclinD1与P16的表达与胶质瘤恶性进程和复发密切相关。     

人脑胶质瘤中p16,p15基因分子的病理学研究

目的:探讨p16、p15基因改变、蛋白表达与脑胶质瘤组织病理的相互关系。方法:应用PCR、银染PCR-SSCP及免疫组化技术检测68例脑胶质瘤中p16、p15基因变化和蛋白表达情况。结果:显示脑胶质瘤中p16、p15基因缺失和P16蛋白丢失主要见于Ⅱ~Ⅳ级肿瘤中,而PCR-SSCP分析未见p16、p15基因点突变。结论:表明脑胶质瘤中p16、p15基因改变是以缺失为主,该基因功能的丧失促进了肿瘤细胞由良性向恶性的演进过程;P16蛋白表达状态可作为判断脑胶质瘤恶性程度及预后的指标。     

人脑星形细胞瘤中p57kip2、cyelinD1的表达及相关性研究

目的探讨p57kip2蛋白、cyclinD1蛋白在人脑星形细胞瘤中的表达情况及其临床意义。方法采用免疫组织化学sP法检测p57kip2、cyclinD1在48例人脑星形细胞瘤和20例正常脑组织中的表达。结果在48例星形细胞瘤中,p57kip2蛋白阳性率为33．3％,显著低于正常脑组织80％。p57kip2蛋白表达在低度恶性（Ⅰ～Ⅱ级）组显著高于高度恶性（Ⅲ～Ⅳ级）组,生存时间≥2年组显著高于〈2年组。星形细胞瘤中cyclinD1蛋白阳性率为62．5％,显著高于正常脑组织15％。cyclinD1蛋白表达在高度恶性（Ⅲ一Ⅳ级）组显著高于低度恶性（Ⅰ一Ⅱ级）组,生存时间〈2年组显著高于≥2年组。p57kip2蛋白的表达与cyclinDI蛋白的表达存在相关。结论p57kip2蛋白和cyctinD1蛋白在星形细胞瘤的发生、发展中起重要作用。且与肿瘤的分化程度、患者预后密切相关。     

胶质瘤中cyclinD1和p57/Kip2蛋白的表达及意义

目的探讨p57/Kip2和细胞周期素cyclinD1在人脑胶质瘤中的表达及意义。方法收集54例胶质瘤和12例正常脑组织标本,应用免疫组化方法检测胶质瘤组织及其正常脑组织中p57/Kip2和cyclinD1蛋白的表达水平。结果免疫组化方法结果显示胶质瘤组织中cyclinD1蛋白水平显著高于正常脑组织,而p57/Kip2的表达水平显著低于正常脑组织,且Pearson相关系数检验提示,胶质瘤组织中p57/Kip2和cyclinD1蛋白的表达水平呈负相关(P0.01)。结论 p57/Kip2胶质瘤组织中表达显著下调,cyclinD1蛋白在胶质瘤组织中异常高表达,且二者表达水平呈显著负相关(r=-0.782,P0.01)。     

细胞周期相关蛋白的表达及其DNA含量分析对脑胶质瘤手术边界的判定意义

一、材料与方法13例脑胶质瘤手术标本,共计39个不同部位(肿瘤中心,边缘及周边组织)应用激光扫描细胞分析仪(LSC)将手术组织标本涂片PI染色后,用于细胞周期和DNA含量分析。术后用同一标本进行免疫组化方法对p53蛋白,细胞周期蛋白的表达进行分析。二、结果1.细胞周期及DNA含量测定,其不同部位的倍体分布和DNA指数不尽相同。2.不同部位的胶质瘤细胞周期相关蛋白,cyclinB1,cyclinD1,p53蛋白表达的阳性率不同。三、讨论Cyclins及其激活的p53在控制细胞周期进程的过程中起重要作用。Cyclins表达水平能够提供肿瘤增值的信息,而Cyclins和p53…     

人脑胶质瘤中β-catenin的表达与细胞增殖相关性研究

目的:探讨人脑胶质瘤中βcatenin的表达及与细胞增殖的相关性。方法:用免疫组化法观察了47例胶质瘤标本βcatenin、cyclinD1、增殖细胞核抗原(PCNA)的表达,并分析其相关性。结果:在胶质瘤中βcatenin、cyclinD1、PCNA均随肿瘤恶性程度增高而增高(P分别为0.017、0.017、0.027),相关分析发现βcatenin、cyclinD1、PCNA的表达两两相关(P<0.001,P<0.001和P=0.005)。结论:βcatenin表达水平的异常与胶质瘤细胞周期调节紊乱、增殖指数上升有关,因此可能是控制肿瘤细胞增殖活性的候选基因之一。     

脑胶质瘤患者血清miR-27b-3p水平与术后复发的相关性分析

目的 分析脑胶质瘤患者血清miR-27b-3p水平与术后复发的相关性。方法 选取安徽医科大学第二附属医院及安徽省立医院于2020-01—2022-12接受手术治疗的脑胶质瘤患者共65例为研究对象,同期收治的颅脑损伤患者25例纳入对照组。脑胶质瘤患者手术完成2周后测定患者血清miR-27b-3p水平。术后随访6个月,将脑胶质瘤患者分为复发组（n=17）及未复发组（n=48）,分析脑胶质瘤患者术后复发的独立危险因素及血清miR-27b-3p在术后复发中的预测价值。结果脑胶质瘤组患者血清miR-27b-3p表达水平（4.57±1.38）显著低于颅脑损伤组（9.46±1.97）(P<0.001)。肿瘤直径≥4.5 cm、WHO分级Ⅲ～Ⅳ级、手术未完全切除及miR-27b-3p低表达是脑胶质瘤患者术后复发的独立危险因素（P<0.05）。肿瘤直径≥4.5 cm及WHO分级Ⅲ～Ⅳ级患者血清miR-27b-3p水平显著低于肿瘤直径<4.5 cm及WHO分级Ⅰ～Ⅱ级的患者（P<0.05）。血清miR-27b-3p对脑胶质瘤患者术后复发具有较高的预测价值,其曲线下面积（AUC）为0...     

人脑胶质瘤中Livin、p53的表达及其与肿瘤恶性程度的关系

目的 探讨Livin、p53在不同级别人脑胶质瘤中的表达及其与肿瘤恶性程度之间的关系.分析二者在胶质瘤细胞凋亡过程中的信号转导机制.方法 应用免疫组织化学技术检测Livin、p53蛋白在41例人脑胶质瘤和10例正常脑组织中的表达.结果 Livin、p53蛋白在10例正常脑组织中均不表达,在41例胶质瘤组织中表达率分别为87.8%和41.5%.Livin和p53蛋白在低级别胶质瘤中表达较低,在高级别胶质瘤中表达较高,两组比较差异有统计学意义(P＜0.05).Spearman等级相关分析显示,Livin蛋白与p53蛋白表达呈正相关(r=1.000,P＜0.01).结论 Livin和p53在人脑胶质瘤组织中表达上调,细胞凋亡受到抑制,引起肿瘤恶性增殖,与胶质瘤病程发展、恶性程度明显相关,这可能是胶质瘤恶性增殖的一个机制.     

p16在星形胶质细胞瘤患者生存分析中的意义

目的探讨p16在星形胶质细胞瘤患者生存分析中的意义。方法采用免疫组化方法检测p16、Rb、细胞周期素D1(cyclinD1)及Ki-67蛋白在62例星形胶质细胞瘤中的表达,对患者进行随访,并结合临床和影像学资料进行生存分析,研究p16的预后意义。结果单因素分析表明p16阴性病例术后生存时间较阳性者明显为短(Logrank检验,P<0.001),而这种差别在卡诺夫斯基机能状态(KPS)评分<70分、复发性肿瘤、Rb和cyclinD1蛋白阴性的病例中不存在;p16不同表达强度的患者之间预后也有差别;但多因素COX模型分析显示p16不是独立的预后因子(P=0.06)。结论p16是能反映星形胶质细胞瘤恶性生物学行为的分子标志物之一,对星形胶质细胞瘤具有初步判断预后的价值,但不是独立的预后因子。     

沉默lncRNA SLC16A1-AS1对脑胶质瘤细胞恶性生物学行为的影响

目的 探讨沉默长链非编码RNA(lncRNA)SLC16A1-AS1对脑胶质瘤细胞恶性生物学行为的影响。方法 PCR检测2021年5月至2023年1月手术切除的62例脑胶质瘤组织lncRNA SLC16A1-AS1、微小RNA(miR)-584-5p以细胞外蛋白调节激酶1(MAPK1)m RNA,免疫印迹法检测MAPK1蛋白表达;以瘤旁组织（距离肿瘤边缘>2 cm）作为正常脑组织。从胶质瘤组织中分离、培养胶质瘤细胞,进行CD133、Neatin免疫荧光染色鉴定;转染不同质粒沉默lncRNA SLC16A1-AS1、上调或下调miR-584-5p表达;应用CCK-8法、划痕实验、Transwell实验和流式细胞术检测细胞增殖、迁移、侵袭和凋亡情况;免疫印迹法检测细胞MAPK1、细胞周期素D1(CyclinD1)、基质金属蛋白酶（MMP）-2、caspase-3蛋白表达;双荧光素酶报告基因实验验证lncRNA SLC16A1-AS1、miR-584-5p和MAPK1的靶向关系。结果 胶质瘤组织lncRNA SLC16A1-AS1、MAPK1呈高表达（P<0.05）,miR-58...     

Establishment and partial characterization of five malignant glioma cell lines

Five malignant glioma cell lines (YMG1, 2, 3, 4, and 5) were established from surgical specimens obtained from patients with glioblastoma or anaplastic astrocytoma, and these lines were partially characterized. Three glioma cell lines (YMG1, 3, and 5) were weakly positive for GFAP by Western blot analysis and two cell lines were negative. S‐100 protein was positive in all glioma cell lines. The expression of p53, p16, p15, cyclin‐dependent kinase 4 (CDK4), and EGF receptor (EGFR) proteins was examined by Western blotting. YMG1 and 2 cell lines showed accumulation of p53 protein and loss of p16 and p15 expression. YMG3 and 4 showed accumulation of p53 protein and expression of p16 and p15 proteins. YMG5 revealed weak expression of p53 protein, suggesting wild‐type p53, and loss of p16 and p15 expression. All cell lines expressed various levels of CDK4 protein. YMG1, 2, and 3 showed higher EGFR protein expression and YMG4 and 5 showed lower EGFR expression compared to U251 glioblastoma cells, which express high levels of EGFR. Fluorescence in situ hybridization analysis for EGFR gene expression did not show any amplification in the glioma cell lines. Immunohistochemical studies revealed that the patterns of p53 and EGFR expressions in the original tumor tissues were mostly correlated with those in the malignant glioma cell lines. These results suggest that the characteristics of p53 and EGFR expression in the malignant glioma cell lines were passed over from the original tumor tissues. These newly established malignant glioma cell lines can be used for further analysis of the mechanisms of tumor growth and progression.     

PI3K/AKT/mTOR信号转导通路相关蛋白在脑胶质瘤中的表达及临床意义

目的研究PI3K/AKT/mTOR信号转导通路相关蛋白PI3K、mTOR、PTEN在脑胶质瘤中的表达及临床意义。方法采用免疫组化Envision二步法检测75例患者的脑胶质瘤标本(胶质瘤组,其中肿瘤分级Ⅱ级30例,Ⅳ级45例)及10名正常人(正常对照组)脑组织PI3K、mTOR、PTEN蛋白的表达,并对脑胶质瘤患者进行生存的相关分析。结果 PI3K、mTOR蛋白在胶质瘤组的阳性率显著高于正常对照组(均P<0.01),PTEN阳性率显著低于正常对照组(P<0.05)。Ⅱ级脑胶质瘤标本中PI3K、mTOR蛋白阳性率显著低于Ⅳ级(均P<0.01),PTEN阳性率显著高于Ⅳ级(P<0.05)。PTEN与PI3K、mTOR蛋白在胶质瘤中的表达分别呈负相关(r=-0.565,P=0.000;r=-0.322,P=0.005);PI3K与mTOR的表达呈正相关(r=0.456,P=0.000)。单因素分析显示,年龄、肿瘤级别、术后放化疗及PI3K蛋白表达影响患者术后的生存时间(r=-0.306,r=-0.422,r=0.392,r=-0.320;均P<0.05)。多因素回归分析显示,肿瘤级别、术后放化疗及PI3K蛋白表达为影响胶质瘤患者预后的独立因素(χ2=17.568,χ2=4.171,χ2=4.427;均P<0.05)。结论脑胶质瘤PI3K、mTOR的表达增高,PTEN的表达降低,并与肿瘤的恶性程度有关。肿瘤级别、术后放化疗及PI3K蛋白表达水平是影响胶质瘤患者预后的独立因素。     

Chromosomal alterations,prognostic factors,and targeted molecular therapies for malignant meningiomas

Meningiomas are the second most common intracranial neoplasm in adults and originate from arachnoidal cap cells. Malignant meningiomas are resistant to conventional treatments such as surgery, chemotherapy, and radiotherapy. Unlike benign meningiomas, atypical and anaplastic tumors generally display more complex karyotypes associated with aggressive behavior. While these chromosomal anomalies are associated with greater malignancy in meningiomas, the specific genes involved remain unknown. Malignant meningiomas are characterized by increased tumor aggressiveness, rapid recurrence, local invasion, atypical histological appearance, and a high mitotic index. Potential prognostic factors include extent of resection, treatment with radiotherapy or stereotactic radiosurgery, Ki-67/MIB-1 labeling index, p53 overexpression, percentage of tumor cells in the S-phase, telomerase activity, and numerous genetic expression profiles. A greater understanding of prognostic factors and molecular markers involved in critical signaling pathways may aid in the identification of novel therapeutic targets. As such, further studies are needed to establish reliable prognostic factors and develop more effective treatments for malignant meningiomas.     

转染外源性p16基因对恶性胶质瘤生长抑制作用的动物体内实验研究

目的 :探讨p16基因在体内对恶性胶质瘤的生长抑制作用。方法 :将外源性p16基因导入C6 细胞内 ,应用立体定向技术将C6细胞种植于SD大鼠尾状核头部 ,用核磁共振 (MR)扫描技术 ,动态观察颅内肿瘤生长情况。并通过免疫组化、原位杂交和细胞凋亡检测肿瘤细胞的增殖活性。结果 :转染组和治疗组大鼠生存期较对照组明显延长。治疗组肿瘤随时间的延长逐渐缩小。免疫组化显示转染组和治疗组P16蛋白表达明显增强。原位杂交和细胞凋亡检测表明 ,转染组和治疗组大鼠肿瘤细胞增殖活性降低。结论 :p16基因在体内有抑制恶性胶质瘤生长的作用 ;瘤体内注入p16cDNA质粒 脂质体复合物 ,可使肿瘤生长受到明显抑制 ,并使多数肿瘤消失     

PTTG、p16和cyclinD1的表达与垂体腺瘤侵袭性的关系

目的通过对垂体腺瘤中垂体瘤转化基因(pituitarytumortransforminggene,PTTG)、周期素依赖激酶抑制因子p16(cyclin-de-pendentkinaseinhabitor,p16Ink4)mRNA和蛋白以及细胞周期素D1(cyclinD1)蛋白表达的检测和相关性比较,探讨PTTG、p16和cyclinD1的表达与垂体腺瘤细胞周期调控和侵袭性之间的关系。方法将30例垂体腺瘤手术标本分为侵袭组和非侵袭组,采用RT-PCR法检测PTTG和p16mRNA的表达,免疫组化检测PTTG、P16和cyclinD1蛋白的表达,分析侵袭组和非侵袭组PTTG、p16和cyclinD1表达水平的差异和相关性。结果在垂体腺瘤中,p16mRNA表达缺失或低下的发生率为73.3%,以p16mRNA缺失和表达分组,PTTGmRNA的表达水平在垂体腺瘤p16mRNA缺失组和表达组之间无显著性差异;侵袭组垂体腺瘤的PTTG、cyclinD1蛋白表达较非侵袭组显著性增高;且二者表达程度呈正相关;P16蛋白的表达在侵袭组垂体腺瘤显著减低,并与PTTG和cyclinD1蛋白表达程度呈负相关。结论p16mRNA在垂体腺瘤表达的缺失或低下与垂体腺瘤侵袭性无关。PTTG、p16和cyclinD1蛋白表达的差异与细胞周期调控相关,可作为垂体腺瘤侵袭性的评估指标。     

Diagnostic utility of IDH1- and p53-mutation analysis in secondary gliosarcoma

We report on a 47-year-old woman in whom an anaplastic astrocytoma was resected in 2006. Postoperative radiation had to be interrupted because of a wound infection necessitating explantation of the infected bone flap and implantation of a titanium mesh. Subsequently, radiation therapy was completed and temozolomide was administered for 45 cycles. In the beginning of 2010 a new contrast enhancing mass was seen in the former tumor region. The mass was subtotally excised and showed no histomorphological similarity to the first lesion but represented a highly pleomorphic and mainly sarcomatoid differentiated malignant tumor. The lack of expression of GFAP or MAP-2 raised the question of a secondary malignancy, however, molecular genetic analysis of IDH1 and p53 revealed the same mutations in the anaplastic astrocytoma from 2006 as in the sarcomatoid tumor operated in 2010. Furthermore, accumulation of mutated IDH1 and TP53 protein could be demonstrated immunohistochemically. Thus, the second tumor represented the rare instance of recurrence of an anaplastic astrocytoma as a secondary gliosarcoma and a second malignant neoplasm was ruled out. The postoperative therapy and the inflammation might have contributed to the severe change in morphological phenotype of the glioma.     

p16基因CpG岛甲基化与胶质瘤生物学特性的关系

目的：研究p16基因CpG岛甲基化与胶质瘤恶性程度分级及肿瘤细胞增殖活性的关系。方法：应用半巢式甲基化特异性多聚酶链反应（MSP）检测40例不同级别的胶质瘤组织标本中p16基因CpG岛甲基化状态。免疫组化SP法分析肿瘤组织p16蛋白和Ki-67抗原的表达情况。结果：肿瘤组织甲基化发生率为42.5%（17/40）,p16蛋白表达缺失率为72.5%（29/40）,其中55.2%（16/29）缺失与甲基化有关（P=0.0085）。甲基化发生率随胶质瘤恶性程度增加有增高趋势（χ2=11.4288,P=0.0007）。甲基化阳性者中Ki-67抗原增殖指数明显高于甲基化阴性者（P〈0.05）。结论：p16基因CpG岛甲基化导致该基因灭活是胶质细胞恶性增生的主要机制之一。     

The positive correlation between DJ‐1 and β‐catenin expression shows prognostic value for patients with glioma

The relationship between DJ‐1 and β‐catenin, and its impact on the prognosis for glioma patients has not been fully understood. This study determined the effect of DJ‐1 on β‐catenin and the prognostic significance of this interaction in glioma patients. We collected tumor specimens from 88 glioma patients and determined the expression of DJ‐1, β‐catenin and PTEN by using immunohistochemical staining. The involvement of DJ‐1 and β‐catenin in glioma cell lines was evaluated by immunohistochemistry and Western blotting. High DJ‐1 expression (37.5%) and high β‐catenin expression (34.1%) in glioma specimens were significantly associated with high grade and poor prognosis in glioma patients. However, only high levels of DJ‐1 (P = 0.014) was a strong independent prognostic factor, correlated with a reduced overall survival time. In vitro DJ‐1 expression was positively correlated with the expression levels of β‐catenin and p‐Akt, and negatively correlated with PTEN expression in U87, U251 MG, SWO‐38 and SHG44 human glioma cell lines. After the knockdown of DJ‐1, Akt, p‐Akt or β‐catenin expression levels were not affected in the PTEN‐null cell lines (U87 and U251 MG). However, in the SWO‐38 cell line, which has wild‐type PTEN protein, the level of PTEN increased while Akt/p‐Akt and β‐catenin levels were reduced. Furthermore, β‐catenin staining weakened in SWO‐38 cells after DJ‐1 levels decreased according to immunocytochemical analysis. In conclusion, DJ‐1 and β‐catenin may contribute to the development and recurrence of glioma and are valuable prognostic factors for glioma patients. DJ‐1 may regulate β‐catenin expression via PTEN and p‐Akt.     

HGF、c-Met、PCNA、CD34表达与胶质瘤恶性程度及预后因素的研究

目的研究肝细胞生长因子（HGF）、肝细胞生长闪子受体（c—Met）、增殖细胞核抗原（PCNA）、CD34在胶质瘤的表达，并结合多种临床因素探讨其与肿瘤恶性程度及预后的关系。方法用原位杂交法检测68例胶质瘤中HGF、c-MetmRNA的表达，用SP免疫组化技术检测PCNA、CD34在肿瘤巾的表达。并对可能影响预后的㈥素进行统计学分析。结果胶质瘤HGF、c-Met、PCNA的表达在高低级别组之间存在显著差异（P〈0．05）。Logistic逻辑回归单因素分析显示，患者年龄、切除范嗣、恶性程度、术前KPS评分、瘤周水肿、术后放疗、HGF表达、c-Met表达、PCNA表达、MVD对3年存活率有意义；多阕素分析表明，肿瘤的恶性程度、术前KPS评分、MVD、PCNA及c-Met基因的表达是影响预后的主要因素。结论HGF、c-Met、PCNA在胶质瘤中的表达与其恶性程度相关，肿瘤的恶性程度、术前KPS评分、MVD、PCNA及c-Met基因的表达可作为考察胶质瘤患者预后的重要指标。